text: The two main clinical outcomes of acute p-i reactions are MPE/DRESS on one hand, and SJS/TEN on the other hand. In MPE/DRESS patients, high numbers of circulating, atypical (activated) lymphocytes and high levels of various cytokines can be found in the circulation. In vitro drug stimulation reveals a proliferating, high cytokine secreting, cytotoxic CD4 and CD8 T cell reaction to the incriminated drug, which sometimes can be detected for many years.  
  Quite in contrast, patients with SJS/TEN may show lymphopenia, just the blister fluids are full of mainly CD8/NK+, cytotoxic T cells, which are able to kill keratinocytes. Cytotoxic molecules (granzyme B, perforin, granulysin) can be detected in vivo in blood and the blister fluid in the first few days of the disease. During the acute disease (1–2 weeks), the T cells still react in in vitro assays, but after 3–4 weeks, the CD8 cell compartment, which is considered to be the main responsible cell population for the disease, appears to be exhausted and are refractory to drug stimulation. How this CD8 exhaustion is achieved is unknown.